Longitudinal population-level HIV epidemiologic and genomic surveillance highlights growing gender disparity of HIV transmission in Uganda.

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep-sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted: whereas HIV transmission to girls and women (aged 15-24 years) from older men declined by about one-third, transmission to women (aged 25-34 years) from men that were 0-6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programmes to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men's health in Africa.

Dating reservoir formation in virologically suppressed people living with HIV-1 in Rakai, Uganda.

The timing of the establishment of the HIV latent viral reservoir (LVR) is of particular interest, as there is evidence that proviruses are preferentially archived at the time of antiretroviral therapy (ART) initiation. Quantitative viral outgrowth assays (QVOAs) were performed using Peripheral Blood Mononuclear Cells (PBMC) collected from Ugandans living with HIV who were virally suppressed on ART for >1 year, had known seroconversion windows, and at least two archived ART-naïve plasma samples. QVOA outgrowth populations and pre-ART plasma samples were deep sequenced for the pol and gp41 genes. The bayroot program was used to estimate the date that each outgrowth virus was incorporated into the reservoir. Bayroot was also applied to previously published data from a South African cohort. In the Ugandan cohort (n = 11), 87.9 per cent pre-ART and 56.3 per cent viral outgrowth sequences were unique. Integration dates were estimated to be relatively evenly distributed throughout viremia in 9/11 participants. In contrast, sequences from the South African cohort (n = 9) were more commonly estimated to have entered the LVR close to ART initiation, as previously reported. Timing of LVR establishment is variable between populations and potentially viral subtypes, which could limit the effectiveness of interventions that target the LVR only at ART initiation.

Timing for maximum anaesthetic effect of topical cream during early infant circumcision (EIC) in Rakai, Uganda.

Objectives: The objective of this study is to determine the optimal timing for device-based infant circumcision under topical anaesthesia. Subjects/patients: We include infants aged 1-60 days who were enrolled in a field study of the no-flip ShangRing device at four hospitals in the Rakai region of south-central Uganda, between 5 February 2020 and 27 October 2020. Methods: Two hundred infants, aged 0-60 days, were enrolled, and EMLA cream was applied on the foreskin and entire penile shaft. The anaesthetic effect was assessed every 5 min by gentle application of artery forceps at the tip of the foreskin, starting at 10 min post-application until 60 min, the recommended time to start circumcision. The response was measured using the Neonatal Infant Pain Scale (NIPS). We determined the onset and duration of anaesthesia (defined as <20% of infants with NIPS score >4) and maximum anaesthesia (defined as <20% of infants with NIPS score >2). Results: Overall, NIPS scores decreased to a minimum and reversed before the recommended 60 min. Baseline response varied with age, with minimal response among infants aged 40 days. Overall, anaesthesia was achieved after at least 25 min and lasted 20-30 min. Maximum anaesthesia was achieved after at least 30 min (except among those aged >45 days where it was not achieved) and lasted up to 10 min. Conclusion: The optimal timing for maximum topical anaesthesia occurred before the recommended 60 min of waiting time. A shorter waiting time and speed may be efficient for mass device-based circumcision.

Exploring HIV/AIDS investigator perceptions of equity within research partnerships between low-and middle-income and high-income countries: a pilot survey.

BACKGROUND: Recommendations for research partnerships between low- and middle-income countries (LMICs) and high-income countries (HICs) stress the importance of equity within the collaboration. However, there is limited knowledge of the practical challenges and successes involved in establishing equitable research practices. This study describes the results of a pilot survey assessing key issues on LMIC/HIC partnership equity within HIV/AIDS research collaborations and compares perspectives of these issues between LMIC- and HIC-based investigators. METHODS: Survey participants were selected using clustered, random sampling and snowball sampling. Responses were compared between LMIC and HIC respondents using standard descriptive statistics. Qualitative respondent feedback was analyzed using a combination of exploratory and confirmatory thematic analysis. RESULTS: The majority of categories within four themes (research interests and resources; leadership, trust, and communication; cultural and ethical competence; representation and benefits) demonstrated relative consensus between LMIC and HIC respondents except for 'lack of trust within the partnership' which was rated as a more pronounced challenge by LMIC respondents. However, subcategories within some of the themes had significant differences between respondent groups including: equitable setting of the research agenda, compromise within a partnership, the role of regulatory bodies in monitoring partnerships for equity, and post-study access to research technology. CONCLUSIONS: These efforts serve as a proof-of-concept survey characterizing contemporary issues around international research partnership equity. The frequency and severity of specific equity issues can be assessed, highlighting similarities versus differences in experiences between LMIC and HIC partners as potential targets for further discussion and evaluation.

Longitudinal population-level HIV epidemiologic and genomic surveillance highlights growing gender disparity of HIV transmission in Uganda.

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted, while HIV transmission to girls and women (aged 15-24 years) from older men declined by about one third, transmission to women (aged 25-34 years) from men that were 0-6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programs to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men's health in Africa.

Makerere's contribution to the development of a high impact HIV research population-based cohort in the Rakai Region, Uganda.

Longitudinal population-based cohort studies can provide critical insights on temporal, spatial and sociodemographic changes in health status and health determinants that are not obtained by other study designs. However, establishing and maintaining such a cohort study can be challenging and expensive. Here, we describe the role of Makerere University in the development and conduct of such a cohort. We chronicle the first academia-led reports of HIV in East Africa; how this led to initiation of the Rakai Community Cohort Study in 1988, the first and oldest HIV cohort in sub-Saharan Africa; its impact on HIV prevention, care and treatment; how the cohort has been maintained; and opportunities, challenges, and future directions including non-communicable diseases.

Women's support for voluntary medical male circumcision in fishing communities on the shores of Lake Victoria, Uganda.

BACKGROUND: Women's support can improve uptake of voluntary medical male circumcision (VMMC). We assessed the level of women's support for VMMC and associated factors in fishing settlements on the shores of Lake Victoria in Uganda, to inform interventions aimed at increasing the uptake of safe male circumcision services in such high-risk populations. METHODS: We conducted a cross-sectional study, employing mixed methods of data collection, at Kasenyi and Kigungu landing sites in April 2018. We included women aged 18-49 years, who had stayed at the landing sites for ≥3 months. We obtained qualitative data using focus group discussions (FGDs), and interviewer-administered semi-structured questionnaires for quantitative data. The tool captured demographic characteristics, community factors including cultural norms and beliefs, women's experiences, and health facility-related factors. The dependent variable was derived from the response to the question: "Would you encourage your partner/husband to go for VMMC?", and used as a proxy for support of VMMC. We used modified Poisson regression to identify factors associated with women's support for VMMC. Qualitative data were analysed using thematic content analysis. RESULTS: We enrolled 313 women with a mean age of 28 (SD±6.8) years. Of the 313 women, 230 (73.5%) supported VMMC. Belief that VMMC increases penile hygiene (Adjusted prevalence ratio [aPR]=1.9; CI: 1.8-3.2), performing VMMC for religious reasons (aPR=1.9; CI: 1.8-2.9), preference for a circumcised man (aPR=1.3; CI: 1.2-1.5), belief that vaginal fluids facilitate wound healing (aPR=1.9; CI: 1.3-2.7), and knowledge about when a man can resume sex (4 weeks) after circumcision (aPR=2.1; CI: 1.8-3.3) were associated with women's support for VMMC. FGDs revealed that women were not adequately involved in VMMC activities for decision making. CONCLUSION: The support for VMMC was high among women in the fishing communities. However, women perceived they were not involved in decision-making for VMMC and had several misconceptions, including a belief that vaginal fluids facilitate wound healing. The Ministry of Health and VMMC implementing partners should devise strategies to increase sensitization and involvement of women in VMMC decision-making without slowing service uptake.

Severe Acute Respiratory Syndrome Coronavirus-2 seroprevalence in South-Central Uganda, during 2019-2021.

BACKGROUND: Globally, key subpopulations such as healthcare workers (HCW) may have a higher risk of contracting SARS-CoV-2. In Uganda, limited access to Personal Protective Equipment and lack of clarity on the extent/pattern of community spread may exacerbate this situation. The country established infection prevention/control measures such as lockdowns and proper hand hygiene. However, due to resource limitations and fatigue, compliance is low, posing continued onward transmission risk. This study aimed to describe extent of SARS-CoV-2 seroprevalence in selected populations within the Rakai region of Uganda. METHODS: From 30th November 2020 to 8th January 2021, we collected venous blood from 753 HCW at twenty-six health facilities in South-Central Uganda and from 227 population-cohort participants who reported specific COVID-19 like symptoms (fever, cough, loss of taste and appetite) in a prior phone-based survey conducted (between May and August 2020) during the first national lockdown. 636 plasma specimens collected from individuals considered high risk for SARS-CoV-2 infection, prior to the first confirmed COVID-19 case in Uganda were also retrieved. Specimens were tested for antibodies to SARS-CoV-2 using the CoronaChek™ rapid COVID-19 IgM/IgG lateral flow test assay. IgM only positive samples were confirmed using a chemiluminescent microparticle immunoassay (CMIA) (Architect AdviseDx SARS-CoV-2 IgM) which targets the spike protein. SARS-CoV-2 exposure was defined as either confirmed IgM, both IgM and IgG or sole IgG positivity. Overall seroprevalence in each participant group was estimated, adjusting for test performance. RESULTS: The seroprevalence of antibodies to SARS-CoV-2 in HCW was 26.7% [95%CI: 23.5, 29.8] with no difference by sex, age, or cadre. We observed no association between PPE use and seropositivity among exposed healthcare workers. Of the phone-based survey participants, 15.6% [95%CI: 10.9, 20.3] had antibodies to SARS-CoV-2, with no difference by HIV status, sex, age, or occupation. Among 636 plasma specimens collected prior to the first confirmed COVID-19 case, 2.3% [95%CI: 1.2, 3.5] were reactive. CONCLUSIONS: Findings suggest high seroprevalence of antibodies to SARS-CoV-2 among HCW and substantial exposure in persons presenting with specific COVID-19 like symptoms in the general population of South-Central Uganda. Based on current limitations in serological test confirmation, it remains unclear whether seroprevalence among plasma specimens collected prior to confirmation of the first COVID-19 case implies prior SARS-CoV-2 exposure in Uganda.

Severe Acute Respiratory Syndrome Coronavirus-2 Seropositivity in South-Central Uganda, During 2019 - 2021.

Background: Globally, key subpopulations such as healthcare workers (HCWs) have a higher risk of contracting SARS-CoV-2. In Uganda, limited access to personal protective equipment amidst lack of clarity on the extent and pattern of the community disease burden may exacerbate this situation. We assessed SARS-CoV-2 antibody seroprevalence among high-risk sub-populations in South-central Uganda, including HCWs, persons within the general population previously reporting experiencing key COVID-19 like symptoms (fever, cough, loss of taste and smell) and archived plasma specimens collected between October 2019 â€" 18 th March 2020, prior to confirmation of COVID-19 in Uganda. Methods: From November 2020 - January 2021, we collected venous blood from HCWs at selected health facilities in South-Central Uganda and from population-cohort participants who reported specific COVID-19 like symptoms in a prior phone-based survey conducted (between May to August 2020) during the first national lockdown. Pre-lockdown plasma collected (between October 2019 and March 18 th , 2020) from individuals considered high risk for SARS-CoV-2 infection was retrieved. Specimens were tested for antibodies to SARS-CoV-2 using the CoronaChek TM rapid COVID-19 IgM/IgG lateral flow test assay. IgM only positive samples were confirmed using a chemiluminescent microparticle immunoassay (CMIA) (Architect AdviseDx SARS-CoV-2 IgM) which targets the spike protein. SARS-CoV-2 exposure was defined as either confirmed IgM, both IgM and IgG or sole IgG positivity. Results: The seroprevalence of antibodies to SARS-CoV-2 in HCWs was 21.1% [95%CI: 18.2-24.2]. Of the phone-based survey participants, 11.9% [95%CI: 8.0-16.8] had antibodies to SARS-CoV-2. Among 636 pre-lockdown plasma specimens, 1.7% [95%CI: 0.9-3.1] were reactive. Conclusions: Findings suggest a high seroprevalence of antibodies to SARS-CoV-2 among HCWs and substantial exposure in persons presenting with specific COVID-19 like symptoms in the general population of South-central Uganda. Based on current limitations in serological test confirmation, it remains unclear whether pre-lockdown seropositivity implies prior SARS-CoV-2 exposure in Uganda.

Short Communication: Validation of the Asante HIV-1 Rapid Recency Assay for Detection of Recent HIV-1 Infections in Uganda.

Point of care rapid recency testing for HIV-1 may be a cost-effective tool to identify recently infected individuals for incidence estimation, and focused HIV prevention through intensified contact tracing. We validated the Asante™ HIV-1 rapid recency® assay for use in Uganda. Archived specimens (serum/plasma), collected from longitudinally observed HIV-1 recently and long-term infected participants, were tested with the Asante HIV-1 rapid recency assay per manufacturer's instructions. Previously identified antiretroviral therapy (ART)-naive samples with known seroconversions within 6 months of follow-up were tested in independent laboratories: the Rakai Health Sciences Program (RHSP) and the Uganda Virus Research Institute HIV Reference Laboratory (UVRI-HRL). In addition, samples from participants who seroconverted within 6-18 months and samples from individuals with chronic HIV-1 infection of at least 18 months duration were classified into three categories: ART naive, ART exposed with suppressed viral loads, and ART exposed with detectable viremia. Of the 85 samples seroconverting in ≤6 months, 27 and 42 samples were identified as "recent" by the Asante HIV-1 rapid recency test at the RHSP laboratory and UVRI-HRL, corresponding to sensitivities of 32% and 49%, respectively. There was 72% agreement between the laboratories (Cohen's kappa = 0.481, 95% CI = 0.317-0.646, p < .0001). Specificity was 100% (200/200) among chronically infected ART-naive samples. The Asante HIV-1 rapid recency assay had low sensitivity for detection of recent HIV-1 infections in Uganda, with substantial interlaboratory variability due to differential interpretation of the test strip bands. Specificity was excellent. Assessment of assay performance in other settings is needed to guide decisions on test utility.

Knowledge on voluntary medical male circumcision in a low uptake setting in northern Uganda.

BACKGROUND: Free VMMC services have been available in Uganda since 2010. However, uptake in Northern Uganda remains disproportionately low. We aimed to determine if this is due to men's insufficient knowledge on VMMC, and if women's knowledge on VMMC has any association with VMMC status of their male sexual partners. METHODS: In this cross sectional study, participants were asked their circumcision status (or that of their male sexual partner for female respondents) and presented with 14 questions on VMMC benefits, procedure, risk, and misconceptions. Chi square tests or fisher exact tests were used to compare circumcision prevalence among those who gave correct responses versus those who failed to and if p < 0.05, the comparison groups were balanced with propensity score weights in modified poisson models to estimate prevalence ratios, PR. RESULTS: A total of 396 men and 50 women were included in the analyses. Circumcision was 42% less prevalent among males who failed to reject the misconception that VMMC reduces sexual performance (PR = 0.58, 95% CI 0.38-0.89, p = 0.012), and less prevalent among male sexual partners of females who failed to reject the same misconception (PR = 0.22, 95% CI = 0.07-0.76, p = 0.016). Circumcision was also 35% less prevalent among male respondents who failed to reject the misconception that VMMC increases a man's desire for more sexual partners i.e. promiscuity (PR = 0.65, 95% CI = 0.46-0.92, p = 0.014). CONCLUSION: Misconceptions regarding change in sexual drive or performance were associated with circumcision status in this population, while knowledge of VMMC benefits, risks and procedure was not.

Sexual risk behaviors following circumcision among HIV-positive men in Rakai, Uganda.

OBJECTIVE: To determine whether circumcision of HIV-positive men is associated with increased subsequent sexual risk behaviors which may place their female partners at risk. METHODS: Newly circumcised and uncircumcised HIV-positive men in the Rakai Community Cohort Study were followed from baseline (July 2013-January 2015) to determine trend in sexual risk behaviors and association of circumcision with subsequent sexual risk behaviors at follow up (February 2015-September 2016). Risk behaviors included sexual activity, alcohol before sex, transactional sex, multiple sex partners, casual sex partners, and inconsistent condom use with casual partners. The association was evaluated using modified Poisson regression, and sensitivity analyses were performed after multiple imputation with chained equations for missing data. RESULTS: We identified 538 eligible men, of whom 113(21.0%) were circumcised at baseline and 425(79.0%) were uncircumcised. Men in fishing communities were more likely to be circumcised (p = 0.032) as well as those exposed to targeted HIV messaging (p < 0.001). Overall, 188(34.9%) men were lost to follow up and most were uncircumcised (p = 0.020). Among those followed up, behaviors remained largely unchanged with no differences by circumcision status. Transactional sex appeared to be associated with circumcision in unadjusted analyses (PR = 1.58, 95%CI = 1.01,2.48; p = 0.045, p = 0.05) and adjusted analyses (adj.PR = 1.54, 95%CI = 1.06,2.23; p = 0.022). However, the association was no longer significant in sensitivity analyses after accounting for loss to follow up (adj.PR = 1.43, 95%CI = 0.98,2.08; p = 0.066). No association with circumcision was observed for other sexual risk behaviors. CONCLUSION: We found no association between circumcision of HIV-positive men and subsequent sexual risk behavior.

Efficacy of knowledge and competence-based training of non-physicians in the provision of early infant male circumcision using the Mogen clamp in Rakai, Uganda.

OBJECTIVE: To assess acquisition of knowledge and competence in performing Early Infant Male Circumcision (EIMC) by non-physicians trained using a structured curriculum. SUBJECTS AND METHODS: Training in provision of EIMC using the Mogen clamp was conducted for 10 Clinical Officers (COs) and 10 Registered Nurse Midwives (RNMWs), in Rakai, Uganda. Healthy infants whose mothers consented to study participation were assigned to the trainees, each of whom performed at least 10 EIMCs. Ongoing assessment and feedback for competency were done, and safety assessed by adverse events. RESULTS: Despite similar baseline knowledge, COs acquired more didactic knowledge than RNMWs (P = 0.043). In all, 100 EIMCs were assessed for gain in competency. The greatest improvement in competency was between the first and third procedures, and all trainees achieved 80% competency and retention of skills by the seventh procedure. The median (interquartile range) time to complete a procedure was 14.5 (10-47) min for the COs, and 15 (10-50) min for the RNMWs (P = 0.180). The procedure times declined by 2.2 min for each subsequent EIMC (P = 0.005), and rates of improvement were similar for COs and RNMWs. Adverse events were comparable between providers (3.5%), of which 1% were of moderate severity. CONCLUSION: Competence-based training of non-physicians improved knowledge and competency in EIMC performed by COs and RNMWs in Uganda.